Chronic tubular obstruction leads to a decrease in glomerular blood flow (GBF) and glomerular pressure (GP). The mechanisms involved are not understood. We will determine: (1) whether an increase in Bowman's capsule pressure or a decrease in flow to the macula densa is the signal which leads to the decrase in GBF, (2) whether the vasoconstrictor substances thromboxane A2 or angiotensin II are involved, and (3) whether the response to obstruction is affected by uremia. To determine whether single nephrons atrophy when they are blocked for a prolonged period of time, we will study nephrons functionally and morphologically one day and one week after blockade with solid paraffin. We will also test the idea that obstruction leads to a decrease in GP via a feedback mechanism in acute renal failure. Since glomerular hemodynamics have not been adequately studied in low dose HgCl2 poisoning, we will measure GBF (with microspheres) and GP (directly) in this model of acute renal failure. Finally, we will examine the morphologic and functional consequences of damaging single tubules with HgC12 or serum. These experiments will test the idea that proximal tubule damage reduces glomerular function by a tubuloglomerular feedback mechanism. All experiments will be done in anesthetized rats using primarily micropuncture techniques. We will also study tubular morphology by electron microscopy and nephron microdissection. The proposed studies, by using a combined functional and morphologic analysis, should give us a better idea of how single nephrons respond to obstruction or damage and some of the mechanisms involved. Such information would be valuable in understanding the pathogenesis of many kidney diseases in which tubule injury occurs.